3-52096642-T-C

Variant names:

• chr3-52096642-T-C
• rs1702825064
• NM_015426.5:c.1052A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015426.5(POC1A):​c.1052A>G​(p.Glu351Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POC1A NM_015426.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

Genes affected

POC1A (HGNC:24488): (POC1 centriolar protein A) POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutations in this gene result in short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) syndrome. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19581276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POC1A	NM_015426.5	c.1052A>G	p.Glu351Gly	missense_variant	Exon 10 of 11	ENST00000296484.7	NP_056241.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POC1A	ENST00000296484.7	c.1052A>G	p.Glu351Gly	missense_variant	Exon 10 of 11	1	NM_015426.5	ENSP00000296484.2
POC1A	ENST00000394970.6	c.982-20657A>G		intron_variant	Intron 9 of 9	1		ENSP00000378421.2
POC1A	ENST00000474012.1	c.938A>G	p.Glu313Gly	missense_variant	Exon 10 of 11	2		ENSP00000418968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1052A>G (p.E351G) alteration is located in exon 10 (coding exon 10) of the POC1A gene. This alteration results from a A to G substitution at nucleotide position 1052, causing the glutamic acid (E) at amino acid position 351 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T;.
Eigen	Benign	-0.069
Eigen_PC	Benign	-0.00031
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.054
Sift	Benign	0.034	D;D
Sift4G	Benign	0.088	T;T
Polyphen		0.48	P;.
Vest4		0.34
MutPred		0.21		Loss of glycosylation at P352 (P = 0.0441);.;
MVP		0.31
MPC		0.37
ClinPred		0.75	D
GERP RS		4.2
Varity_R		0.10
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1702825064; hg19: chr3-52130658;